VIDEO: Time of ‘tremendous improvement and innovation’ in multiple myeloma

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There is such a lot of tremendous improvement and innovation happening that it is an exciting time for all of us who treat myeloma and, frankly, also in a way an exciting time for our patients.

So, in multiple myeloma, we have had some major advancements in the past few years that started with the advent of [chimeric antigen receptor (CAR)] T-cell therapy a few years ago. But the new thing that we are noticing is that with CAR-T, the real-world outcomes of CAR T treatment are very similar to the clinical trial outcomes. So that means that whatever we used to know, we noticed in clinical trials, we can almost give the patients similar safety and benefit profile in the real world. So that's an exciting thing. Generally, that doesn't happen with our treatments. In the real world, the benefit actually — there's a significant drop off. Both the CAR T agents are now being reviewed and hopefully coming to earlier lines of therapy. But a request is still with the FDA; we don't have a decision on that. But if that happens, then CAR-T would be available as an opportunity to patients sooner in their treatment paradigm. So that's CAR-T.

Another big event that happened in myeloma over the past couple of years was the advent of what's called bispecific antibodies. And bispecific antibodies are a class agent of drugs that we have had in acute leukemia, in non-Hodgkin lymphoma. But in myeloma now there are three different agents that are available. There is teclistamab [Tecvayli, Janssen] and elranatamab [Elrexfio, Pfizer] that both go against BCMA as the target, and talquetamab [Talvey, Janssen], which goes against GPRC5D. The exciting part is that we are noticing that even if patients have had prior CAR-T or prior BCMA therapy, these BCMA-targeting bispecifics work. So we can actually go after the same target in a different mechanism — that's exciting.

And then talquetamab is obviously a different class of drugs. There are a couple of drugs I would mention that we should keep on our radar because these couple of classes are being developed quite rapidly. One of them is what's called CELMoDs. CELMoDs have something called iberdomide [Bristol Myers Squibb] and mezigdomide [Bristol Myers Squibb] in which data is coming out very nicely, and we even have phase 3 clinical trials ongoing for iberdomide, so something to keep in mind over the horizon.

And then there's always the discussion about BCL2 inhibitors. There have been a couple of negative trials for venetoclax [Venclexta; Genentech, AbbVie], which still brings to question, well, were those trials negative because the agent doesn't work, which all of us think that in patients with translocation 11;14, BCL2 inhibitors should work? But the concern is that maybe the clinical trials were not set up in the best way and so they were not set up to show the best advantage. But there are other BCL2 inhibitors that are being developed and are showing a lot of promise.

So BCL2 inhibitors and CELMoDs to be on the lookout of, CAR-T and bispecifics are here and now, and we are just trying to understand the best how to use them. For example, outpatient, inpatient, how to manage toxicities just so that our patients can get the most benefit.